5-HYDROXYTRYPTAMINE(2) AND 5-HYDROXYTRYPTAMINE(3) RECEPTORS MEDIATE SEROTONIN-INDUCED SHORT-CIRCUIT CURRENT IN PIG JEJUNUM

The purpose of this study was to determine the effect of methysergide, ketanserin, granisetron, cisapride, and renzapride on serotonin (5-hy droxytryptamine-evoked short-circuit current in muscle and myenteric p lexus-stripped pig jejunum using the Ussing chamber technique. Ketanse rin, granisetron, cisapride, and renzapride all reduced the 5-hydroxyt ryptamine-induced increase in short-circuit current by about 50%. Comb ination of ketanserin and granisetron only reduced the 5-hydroxytrypta mine-induced peak increase in short-circuit current by 25%. Cisapride caused a small concentration-dependent increase in short-circuit curre nt. Atropine and hexamethonium both almost completely suppressed the c isapride-induced peak increase in short-circuit current. Ketanserin, g ranisetron, methysergide, and renzapride did not alter the basal short -circuit current. These results suggest that 5-hydroxytryptamine elici ts an increase in short-circuit current by activating epithelial and s ubmucosal 5-hydroxytryptamine(2) and 5-hydroxytryptamine(3) receptor s ubtypes. Furthermore, the short-circuit current-increasing effect of c isapride, is due to activation of at least muscarinic and nicotinic re ceptors.